Positive antineutrophil cytoplasmic antibody serology in patients with lupus nephritis is associated with distinct histopathologic features on renal biopsy.

Class IV-S lupus nephritis is often associated with more necrosis and fewer subendothelial immune deposits compared to class IV-G lupus nephritis, suggestive of necrotising glomerular inflammation found in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. ANCAs are present in a significant proportion of patients with lupus nephritis. Here we determine whether ANCAs are associated with distinct clinical and histopathologic features of lupus nephritis. Thirty-two ANCA-positive biopsies were compared to 222 ANCA-negative biopsies from patients with lupus nephritis. The majority (82%) of ANCA-positive patients had antimyeloperoxidase antibodies. Class IV-S lupus nephritis and glomerular necrosis were significantly more common (36% vs. 16% and 35% vs. 15%, respectively) and isolated Class V lupus nephritis significantly less common (10% vs. 29%) in the ANCA-positive group. ANCA-positive patients had significantly higher dsDNA titers (335u/ml vs. 52u/ml), significantly lower serum C4 concentrations (0.125g/L vs. 0.15g/L) and significantly higher serum creatinine (130µmol/L vs. 84µmol/L) at the time of biopsy. Hence ANCAs appear to influence the histological pattern of lupus nephritis and are associated with worse baseline renal function and more active lupus serology. There was no significant difference in outcome between groups when matched for severity of disease and treatment using propensity scoring. Thus, further studies are needed to examine whether ANCAs in patients with lupus nephritis have a pathogenic role and whether they are associated with worse renal outcomes or are simply a marker of more severe disease.

The Relationship Between Aortic Root Size and Hypertension: An Unsolved Conundrum.

Thoracic aortic aneurysms rupture and dissection are among the most devastating vascular diseases, being characterized by elevated mortality, despite improvements in diagnostic imaging and surgical techniques.An increased aortic root diameter (ARD) represents the main risk factor for thoracic aortic dissection and rupture and for aortic valve regurgitation.Even though arterial hypertension is commonly regarded as a predisposing condition for the development of thoracic aorta aneurysms, the role of blood pressure (BP) as determinant of aortic root enlargement is still controversial. The use of different methods for indexation of ARD may have in part contributed to the heterogeneous findings obtained in the investigations exploring the relationships between ARD and BP. Indeed, the best methods for ARD indexation, as well as the normal values of aortic root size, are still a matter of debate.Several non-hemodynamic factors influence ARD, including age, gender, and anthropometric variables, such as height, weight and their derivatives body surface area (BSA) and body mass index. Of these factors, anthropometric variables have the greatest impact.Several studies documented an association between ARD enlargement, assessed by echocardiography, and some indices of hypertensive target organ damage such as left ventricular hypertrophy, diastolic dysfunction, and carotid intima-media thickening. Recently, we found that ARD, expressed either as absolute values or normalized for BSA (ARD/BSA) or height (ARD/H), was significantly greater in hypertensive subjects with chronic kidney disease (CKD) when compared to their counterparts with normal renal function. Moreover, at univariate analyses estimated glomerular filtration rate (eGFR) showed significant inverse correlations with ARD not indexed and with ARD/BSA and ARD/H. Taking into account the effect of age, sex, duration of hypertension and other potentially confounding factors, in multiple regression analyses, only the association of GFR with ARD/H and that between GFR and ARD/BSA remained statistically significant. The receiver-operating characteristic curve analysis revealed that an estimated GFR of about 50 ml/min/1.73 m2 represents the better threshold to distinguish hypertensive patients with dilated aortic root from those with a normal one.Some population-based studies showed that an enlarged ARD might predict an adverse prognosis, even in absence of aneurysmatic alterations.In the Cardiovascular Health Study, a dilated aortic root was independently associated with an increased risk for stroke, cardiovascular and total mortality in both sexes and with incident congestive heart failure only in men. The relationship between ARD and heart failure has been observed also in the Framingham Heart Study. More recently, the PAMELA (Pressioni Arteriose Monitorate E Loro Associazioni) study demonstrated an independent relationship of ARD/H with incident cardiovascular morbidity and mortality.Although the relationship between BP and aortic root size is still a matter of debate, increasing evidence seems to support the notion that aortic root dilatation, even in absence of aneurysmatic alterations, may be regarded as an hypertensive organ damage paralleling other preclinical markers whose unfavourable prognostic significance is firmly established. Future studies are needed to assess whether or not antihypertensive therapy is able to reduce aortic root dimension and the increased risk associated with its enlargement.

Association between uric acid and renal function in hypertensive patients: which role for systemic vascular involvement?

The role of systemic vascular involvement in mediating the association between serum uric acid (SUA) and renal function in hypertension has not been explored. Main purpose of our study was to investigate whether morphofunctional vascular changes, assessed as carotid intima-media thickness (cIMT) and aortic pulse wave velocity (aPWV), might mediate the association between SUA and renal damage. We enrolled 523 hypertensive subjects with or without chronic kidney disease and divided population into tertiles of SUA based on sex-specific cutoff values. cIMT and aPWV were higher in uppermost SUA-tertile patients when compared to those in the lowest ones (all P < .001). Uricemia strongly correlated with cIMT and aPWV at univariate analysis (P < .001) and with cIMT after adjustment for confounders (P < .001). Adjustment for cIMT attenuated the relationship between SUA and estimated glomerular filtration rate (P = .019). Systemic vascular changes seem partially to mediate the association between SUA and renal function in hypertensive patients, regardless of kidney function.

Association of Renal Resistive Index with Markers of Extrarenal Vascular Changes in Patients with Systemic Lupus Erythematosus.

Recent data suggest that renal hemodynamic parameters obtained by duplex Doppler sonography, especially the intrarenal resistive index (RRI), may be associated with systemic vascular changes. We evaluated the relationships between RRI and arterial stiffness, assessed by aortic pulse wave velocity, and between RRI and subclinical atherosclerosis, assessed by measuring carotid intima-media thickness in patients with systemic lupus erythematosus. We enrolled 39 patients with systemic lupus erythematosus (mean age 39 y) compared with 19 healthy controls, matched for age and sex. Each participant underwent 24 h of ambulatory blood pressure, aortic pulse wave velocity, carotid intima-media thickness and RRI measurements. RRI correlated significantly with aortic pulse wave velocity (r = 0.44, p = 0.006), and with carotid intima-media thickness (r = 0.46, p = 0.003). Both correlations held (p = 0.01), even after correction for age, mean arterial pressure and glomerular filtration rate. Our results suggest that the RRI may be considered a marker of systemic vascular changes and probably a predictor of cardiovascular risk in patients with systemic lupus erythematosus.

Relationship between aortic root size and glomerular filtration rate in hypertensive patients.

OBJECTIVE: Recent studies suggest that enlarged aortic root diameter (ARD) may predict cardiovascular events in absence of aneurysmatic alterations. Little is known about the influence of renal function on ARD. Our study was aimed to assess the relationships between glomerular filtration rate (GFR) and ARD in hypertensive subjects. METHODS: We enrolled 611 hypertensive individuals (mean age: 52 ±â€Š15 years; men 63%). ARD was measured by echocardiography at the level of Valsalva's sinuses using M-mode tracings. It was considered as absolute measure, normalized to body surface area (ARD/BSA) and indexed to height (ARD/H). GFR was estimated by the Chronic Kidney Disease Epidemiology Collaboration equation. The study population was categorized into seven groups: subjects without chronic kidney disease (no CKD) and subjects with increasing severity of CKD (1, 2, 3a, 3b, 4, 5), as proposed by the 2012 Kidney Disease: Improving Global Outcomes guidelines. RESULTS: ARD/BSA and ARD/H showed a stepwise increase from the group with normal renal function to the groups with increasing severity of CKD. GFR correlated significantly with ARD (r = -0.17), ARD/BSA (r = -0.43) and ARD/H (r = -0.35; all P < 0.001). The associations of GFR with ARD/BSA (ß = -0.26; P < 0.001) and ARD/H (ß = -0.13; P = 0.01) held in linear multiple regression analyses, after adjustment for various confounding factors. CONCLUSION: Our study seems to suggest that a reduced renal function may adversely influence ARD. This may contribute to explain the enhanced cardiovascular risk associated with renal insufficiency.

Early Vascular Aging in Normotensive Patients With Systemic Lupus Erythematosus: Comparison With Young Patients Having Hypertension.

Connective tissue diseases, like systemic lupus erythematosus (SLE), are associated with early and accelerated atherosclerosis. Recently, the concept of "early vascular aging" (EVA) has been more widely accepted. Aortic stiffness is one of the important markers of EVA. We evaluated EVA and subclinical atherosclerosis, by measuring aortic pulse wave velocity (aPWV) and carotid intima-media thickness (cIMT), in 50 normotensive patients with SLE (mean age: 39 ± 12 years). We compared these participants with 50 age- and sex-matched patients with essential hypertension (EH) and 20 healthy controls. Each participant underwent 24-hour ambulatory blood pressure monitoring (ABPM), aPWV, and cIMT measurements. Clinic and 24-hour ABPM values were significantly lower in patients with SLE and controls when compared with the participants having EH (all P < .0001), but aPWV and cIMT were significantly lower in the control group when compared with patients having SLE and EH (all P < .001). Overall, patients with SLE and EH had similar cIMT and aPWV values (P = .31 and P = .47, respectively). Our results suggest that SLE has a similar deleterious impact on EVA as EH.

Association of renal resistive index with aortic pulse wave velocity in hypertensive patients.

BACKGROUND: Recent data suggest that renal haemodynamic parameters obtained by duplex Doppler sonography, especially the intrarenal resistive index (RI), may be associated with systemic vascular changes. However, conflicting data exist about the independent relationship between aortic stiffness and RI. The aim of this study was to evaluate the relationship between RI and arterial stiffness, assessed by aortic pulse wave velocity (aPWV), in hypertensive patients. DESIGN: Cross-sectional study. METHODS: We enrolled 264 hypertensive subjects aged between 30 and 70 years. They were divided into two groups, either with normal renal function (n = 140) or with chronic kidney disease (CKD) (n = 124). Each patient underwent assessment of ultrasonographic renal RI and measurement of aPWV through oscillometric device. RESULTS: Patients with renal RI>0.7 showed higher values of aPWV, both in the overall population (p < 0.001) and in the subgroups with (p < 0.01) and without CKD (p < 0.01). Moreover, statistically significant correlations were observed between aPWV and RI in the whole population (r = 0.38, p < 0.001) and in the subgroups with (r = 0.35, p < 0.001) and without CKD (r = 0.31, p < 0.001). These correlations held even after adjustment for several confounding factors in multivariate analyses. CONCLUSIONS: Our results seem to corroborate the concept that the RI may be considered as a marker of systemic vascular changes and therefore a predictor of cardiovascular risk.